An aging alveolar lung model in microgravity

The National Center for Advancing Translational Sciences awarded Brigham & Women's Hospital Inc. a cooperative agreement for $3,504,482 on September 30, 2025, under CFDA 93.350 (National Center for Advancing Translational Sciences). The award funds development of a three-dimensional, immunocompetent, vascularized, and ventilated human alveolar lung model using extracellular matrix-based scaffolds, human induced pluripotent stem cell-derived cells, and a mechanically active microfluidic bioreactor to model pulmonary aging and fibrosis in microgravity conditions aboard the International Space Station-US National Laboratory. The model will enable study of healthy and fibrotic distal lung tissue and serve as a platform for testing therapeutics in a biomimetic, human-based, and pathophysiologically relevant environment.

Performance runs through August 31, 2028, with work performed in Boston, Massachusetts. Brigham & Women's Hospital is a subsidiary of Partners Healthcare System Incorporated (Mass General Brigham).

Two sub-recipients deliver complementary work. University of California, Los Angeles, through its sub-award (awarded March 4, 2026), collaborates on investigating microgravity's impact on alveolar aging by integrating biomimetic matrices and three-dimensional co-culture systems of human induced pluripotent stem cell-derived and primary epithelial, endothelial, mesenchymal, and other alveolar cell types within microfluidic devices to preserve cell phenotypes, function, and cell-cell communication in alveolar architecture. Space Tango LLC (sub-award awarded March 6, 2026), a small disadvantaged business, provides on-orbit research infrastructure through its TangoLab and PAUL platforms and specialized DISCO facility offering conditioned stowage capabilities during experiment completion and descent.

Abstract

The accelerated aging seen in space provides a unique opportunity to model diseases, identify therapeutic targets, and test treatments more quickly than on earth. Space conditions mimic age-related dysfunctions, allowing for faster progression and evaluation of therapies for a number of conditions. Here, we accordingly propose to use extracellular matrix-based scaffolds with interconnected spherical sacs, and human induced pluripotent stem cell-derived cells to develop an immunocompetent, vascularized, and ventilated three-dimensional (3D) model of the human alveolar lung as a truly biomimetic platform for understanding the interplays between pulmonary aging and aging-related disease conditions such as fibrosis, taking the advantage of the microgravity environment at the international space station-US national laboratory. Our central hypothesis is that the use of biomimetic hydrogel matrices with interconnected spherical sacs with suitable stiffness, 3D CO-culture of epithelial, endothelial, immune, and fibroblastic cells, in combination with a mechanically active microfluidic bioreactor, will enable simulating in vivo-like conditions under which different cell types would maintain their correct phenotypes and functions. Such a 3D alveolar lung model will for the first time enable faithful modeling of the healthy and fibrotic distal lung combined with microgravity in a human-based and (patho)physiologically relevant platform, providing a powerful tool for disease-modeling and testing new or existing therapeutics and as such envisaged to have significant and urgent implications in space medicine and more importantly, in benefiting life on earth, and into the future for extended studies on lung diseases.